The asthmatic is exquisitively sensitive to various mediators. We aim to establish the factors causing this hypersensitivity. To achieve this, we will first test to see if the airways are equally sensitive to a number of mediators-methacholine, histamine and prostaglandin F2 Alpha. We also plan to determine if the site of action for these mediators is the same--large or small airways. Furthermore, we would also like to evaluate and see if the hypersensitivity in the asthmatic patient is mediated via the vagus, by seeing if atropine or SCH 1000 can abolish this. We would also like to compare the effect of atropine with that of a beta-2 agonist in preventing the hypersensitive reaction to allergens, as well as mediators. To study the role of serum IgE in the acute asthma reaction, we would like to see if there is any correlation between the serum IgE levels and the bronchial sensitivity in different individuals and also in the same individuals over different seasons. Henderson et al., have shown that serum IgE levels to specific allergens vary from season to season. They are the highest during the allergen season and decrease 3-4 months later. We also plan to study the effect of alpha adrenergic blocking agents in patients with asthma. We have shown the presence of alpha adrenergic receptors in human tracheas in vitro. We would like to see if there is any significant alpha adrenergic activity in vivo in asthmatic airways. All these objectives will be achieved by doing inhalation challenges in asthmatics to the various mediators and recording the flow-volume loops according to the established techniques. The effect of various antagonizing agents will be establised by administering them by aerosol prior to the inhalation challenge on a subsequent day.